CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell–targeted therapies

Marie Le Cann (1) , Françoise Bouhour (2) , Karine Viala (1) , Laurence Simon (1) , Celine Tard (3) , Cédric Rossi (4) , Guillaume Morel (5) , Emmeline Lagrange (6) , Laurent Magy (7) , Alain Créange (8, 9) , Maud Michaud (10) , Jérôme Franques (11) , Andoni Echaniz-Laguna (12) , Jean-Christophe Antoine (13) , Marine Baron (1) , Bertrand Arnulf (14) , Angela Puma (15) , Emilien Delmont (16) , Thierry Maisonobe (1) , Véronique Leblond (1) , Damien Roos-Weil (1)

1 CHU Pitié-Salpêtrière [AP-HP]
2 Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL]
3 LilNCog - Lille Neurosciences & Cognition - U 1172
4 Service d'Hématologie Clinique (CHU de Dijon)
5 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
6 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
7 CHU Trousseau [Tours]
8 ENT - Excitabilité nerveuse et thérapeutique
9 Hôpital Henri Mondor
10 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
11 La Casamance
12 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
13 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
14 AP-HP - Hopital Saint-Louis [AP-HP]
15 CHU Nice - Centre Hospitalier Universitaire de Nice
16 TIMONE - Hôpital de la Timone [CHU - APHM]

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.

Mots clés: CANOMAD; monoclonal gammopathy; MGCS; immunoglobulins; rituximab CANOMAD; chronic ataxic neuropathy; ophthalmoplegia; IgM paraprotein; cold agglutinins and disialosyl antibodies; CIDP; chronic inflammatory demyelinating polyneuropathy; FILO; French Innovative Leukemia Organization; IVIg; intravenous immunoglobulins; MGCS: monoclonal gammopathy of clinical significance; WM; Waldenström macroglobulinemia

Domaines: Médecine humaine et pathologie

Marie Le Cann, Françoise Bouhour, Karine Viala, Laurence Simon, Celine Tard, et al.. CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell–targeted therapies. Blood, 2020, 136 (21), pp.2428-2436. ⟨10.1182/blood.2020007092⟩. ⟨hal-03081893⟩